The airway epithelium is an active cellular layer with ciliary movement to clear materials, the ability to secrete inflammatory effectors, and a biological barrier function that helps protect against pathogenic microorganisms, foreign insults and injury. Compromise of the upper airway epithelium and exposure of the underlying tissue has been associated with many pulmonary diseases, including asthma, bronchitis, and chronic obstructive pulmonary distress syndrome as well as the increased susceptibility to pathogenic microorganisms, which further exacerbates these and other airway diseases. Maintenance of a healthy airway epithelium is through a complicated series of second messenger signaling and communication. Nitric Oxide (NO) is one signaling molecule used in the airway that can have both beneficial and detrimental effects. In this study, primary cultures of airway epithelial tissue and the airway pathogen, Bordetella bronchiseptica, will be used as model systems to elucidate distinct spatiotemporal release of NO by airway epithelial cells as a controlled response to local insults to help defend against cell and tissue damage or as a uncontrolled response that can cause airway cellular damage and allow for progression of airway disease. Established methods in NO research will be used to identify cellular and enzymatic source(s) of NO production in cultured tracheal airway epithelial cells, elucidate the role(s) for NO in Bordetella bronchiseptica cell pathogenesis and determine the bacteriostatic role for NO in airway protection following wounding. Additionally, new NO probes will be used to characterize unique spatiotemporal changes in cellular NO concentration that may elucidate its shift from a preventative to a damaging agent in the airway epithelium.
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